Abstract

OBJECTIVE To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of
an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like
peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1diabetes.

RESEARCH DESIGN AND METHODS A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without
infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin
F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were
measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine,
and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena.
Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia
was almost completely counterbalanced.

RESULTS At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and
IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena.
Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia
was almost completely counterbalanced.

CONCLUSIONS This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and
inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of
GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably
mediated by oxidative stress.